Digital Commons Network^™

Characterization, Antibacterial, Antioxidant, Antidiabetic, And Anti-Inflammatory Activities Of Green Synthesized Silver Nanoparticles Using Phragmanthera Austroarabica A. G. Mill And J. A. Nyberg Extract, Shady Swidan, Dina Khodeer, Sarah Shabayek, Ali Nasr, Roaa Khinkar, Mohammed Aldurdunji, Maryam Ramadan, Jihan Badr

Pharmacy

Introduction: Diabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries.

Methods: The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity.

Results …

Impairment Of Attention Network Function In Posterior Circulation Ischemia-Evidence From The Attention Network Test, Na Li, Chuanjin Li, Xiaohui Xie, Gang Liu, Wendong Zhang, Jin Fan

Publications and Research

Objective:

This study aimed to investigate the effect of posterior circulation ischemia (PCI) on attention network function and to determine whether PCI is holistic or selective attention network deficit and which attention network is affected.

Methods:

Thirty-six PCI patients aged 30 to 75 were assessed using the Attention Network Test and the Mini-Mental State Examination (MMSE). There were no significant differences in age, sex, and education between PCI group and the control group (n = 32). All data were statistically analyzed by SPSS 23.0 software.

Result:

There were no significant difference in the MMSE scores between the two groups. …

Regrowing The Heart, One Tree At A Time, Jeffrey D Steimle, James F Martin

Faculty, Staff and Students Publications

While many animals can completely repair injured tissues, the mammalian heart possesses limited regenerative capabilities. Yan and Cigliola et al. show that AAV-mediated, zebrafish-derived tissue regeneration enhancer elements (TREEs) can direct pro-regenerative gene expression in injured cardiac tissue of mice and pigs that turn off following repair.

Rare Eif4a2 Variants Are Associated With A Neurodevelopmental Disorder Characterized By Intellectual Disability, Hypotonia, And Epilepsy, Maimuna S Paul, Anna R Duncan, Casie A Genetti, Hongling Pan, Adam Jackson, Patricia E Grant, Jiahai Shi, Michele Pinelli, Nicola Brunetti-Pierri, Alexandra Garza-Flores, Dave Shahani, Russell P Saneto, Giuseppe Zampino, Chiara Leoni, Emanuele Agolini, Antonio Novelli, Ulrike Blümlein, Tobias B Haack, Wolfram Heinritz, Eva Matzker, Bader Alhaddad, Rami Abou Jamra, Tobias Bartolomaeus, Saber Alhamdan, Raphael Carapito, Bertrand Isidor, Seiamak Bahram, Alyssa Ritter, Kosuke Izumi, Ben Pode Shakked, Ortal Barel, Bruria Ben Zeev, Amber Begtrup, Deanna Alexis Carere, Sureni V Mullegama, Timothy Blake Palculict, Daniel G Calame, Katharina Schwan, Alicia R P Aycinena, Rasa Traberg, Genomics England Research Consortium, Sofia Douzgou, Harrison Pirt, Naila Ismayilova, Siddharth Banka, Hsiao-Tuan Chao, Pankaj B Agrawal

Faculty, Staff and Students Publications

Eukaryotic initiation factor-4A2 (EIF4A2) is an ATP-dependent RNA helicase and a member of the DEAD-box protein family that recognizes the 5' cap structure of mRNAs, allows mRNA to bind to the ribosome, and plays an important role in microRNA-regulated gene repression. Here, we report on 15 individuals from 14 families presenting with global developmental delay, intellectual disability, hypotonia, epilepsy, and structural brain anomalies, all of whom have extremely rare de novo mono-allelic or inherited bi-allelic variants in EIF4A2. Neurodegeneration was predominantly reported in individuals with bi-allelic variants. Molecular modeling predicts these variants would perturb structural interactions in key protein domains. …

Global Gene Expression Analysis Reveals Complex Cuticle Organization Of The Tribolium Compound Eye, Qing Chen, Arun Kirshna Sasikala-Appukuttan, Zahabiya Husain, Anura Shrivastava, Marla Spain, Edward D Sendler, Bryce Daines, Stefan Fischer, Rui Chen, Tiffany A Cook, Markus Friedrich

Faculty, Staff and Students Publications

The red flour beetle Tribolium castaneum is a resource-rich model for genomic and developmental studies. To extend previous studies on Tribolium eye development, we produced transcriptomes for normal-eyed and eye-depleted heads of pupae and adults to identify differentially transcript-enriched (DE) genes in the visual system. Unexpectedly, cuticle-related genes were the largest functional class in the pupal compound eye DE gene population, indicating differential enrichment in three distinct cuticle components: clear lens facet cuticle, highly melanized cuticle of the ocular diaphragm, which surrounds the Tribolium compound eye for internal fortification, and newly identified facet margins of the tanned cuticle, possibly enhancing …

A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion …

Notch Blockade Specifically In Bone Marrow-Derived Fsp-1-Positive Cells Ameliorates Renal Fibrosis, Yongdong Wu, Ming Liang, Fengzhang Huang, Owen H Cheng, Xiaoguang Xiao, Tae Hoon Lee, Luan Truong, Jizhong Cheng

Faculty, Staff and Students Publications

Background: The infiltration of inflammatory cells during a kidney injury stimulates myofibroblast activation leading to kidney fibrosis. Fibroblast-specific protein 1 (FSP-1) positive cells have been reported as either myofibroblasts or monocytes during tissue fibrosis. The functions of FSP-1+ cells that are associated with the development of renal fibrosis and the signaling pathways that regulate FSP-1+ cell activation have not been well defined. Methods: In mice with unilateral ureteral obstruction (UUO), we characterized FSP-1+ cells and determined the role of the Notch signaling pathway in the activation of bone marrow-derived FSP-1+ cells during kidney fibrosis. Results: In kidneys from mice with …

Treatment Strategies And Mechanisms Associated With The Prevention Of Nash-Associated Hcc By A Toll-Like Receptor 4 Inhibitor, Suet-Ying Kwan, Alyssa N Slayden, Aubrey R Coronado, Rosamaria C Marquez, Huiqin Chen, Peng Wei, Michelle I Savage, Lana A Vornik, Jennifer T Fox, Shizuko Sei, Dong Liang, Heather L Stevenson, Gregory K Wilkerson, Mihai Gagea, Powel H Brown, Laura Beretta

Faculty, Staff and Student Publications

UNLABELLED: We evaluated the cancer preventive efficacy of TAK-242, an inhibitor of Toll-like receptor 4 (TLR4), in a mouse model of hepatocellular carcinoma (HCC) occurring in the context of nonalcoholic steatohepatitis (NASH). We also assessed the cellular events associated with the preventive treatment efficacy. We tested oral administration of TAK-242, at clinically relevant but toxicity-reducing doses and scheduling, in mice with hepatocyte-specific deletion of Pten (HepPten-). The optimal dose and oral gavage formulation of TAK-242 were determined to be 30 mg/kg in 5% DMSO in 30% 2-hydroxypropyl-β-cyclodextrin. Daily oral administration of 30 mg/kg TAK-242 over 18 weeks was well tolerated …

Phase I Dose Escalation Study Of Topical Bexarotene In Women At High Risk For Breast Cancer, Parijatham S Thomas, Anisha B Patel, J Jack Lee, Diane D Liu, Mike Hernandez, Miguel Muzzio, Alejandro Contreras, Valerie Sepeda, Carrie Mays, Diane Weber, Lana A Vornik, Seema A Khan, Eileen Dimond, Brandy M Heckman-Stoddard, Marjorie Perloff, Powel H Brown

Faculty, Staff and Student Publications

Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.

Molecular Mechanisms And Future Implications Of Vegf/Vegfr In Cancer Therapy, Sonia A Patel, Monique B Nilsson, Xiuning Le, Tina Cascone, Rakesh K Jain, John V Heymach

Faculty, Staff and Student Publications

Angiogenesis, the sprouting of new blood vessels from existing vessels, is one of six known mechanisms employed by solid tumors to recruit blood vessels necessary for their initiation, growth, and metastatic spread. The vascular network within the tumor facilitates the transport of nutrients, oxygen, and immune cells and is regulated by pro- and anti-angiogenic factors. Nearly four decades ago, VEGF was identified as a critical factor promoting vascular permeability and angiogenesis, followed by identification of VEGF family ligands and their receptors (VEGFR). Since then, over a dozen drugs targeting the VEGF/VEGFR pathway have been approved for approximately 20 solid tumor …

The Lysosomal Ragulator Complex Activates Nlrp3 Inflammasome In Vivo Via Hdac6, Kohei Tsujimoto, Tatsunori Jo, Daiki Nagira, Hachiro Konaka, Jeong Hoon Park, Shin-Ichiro Yoshimura, Akinori Ninomiya, Fuminori Sugihara, Takehiro Hirayama, Eri Itotagawa, Yusei Matsuzaki, Yuki Takaichi, Wataru Aoki, Shotaro Saita, Shuhei Nakamura, Andrea Ballabio, Shigeyuki Nada, Masato Okada, Hyota Takamatsu, Atsushi Kumanogoh

Duncan NRI Faculty and Staff Publications

The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting …

Feasibility And Preclinical Efficacy Of Cd7-Unedited Cd7 Car T Cells For T Cell Malignancies, Norihiro Watanabe, Feiyan Mo, Rong Zheng, Royce Ma, Vanesa C Bray, Dayenne G Van Leeuwen, Juntima Sritabal-Ramirez, Hongxiang Hu, Sha Wang, Birju Mehta, Madhuwanti Srinivasan, Lauren D Scherer, Huimin Zhang, Sachin G Thakkar, Laquisa C Hill, Helen E Heslop, Chonghui Cheng, Malcolm K Brenner, Maksim Mamonkin

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR)-mediated targeting of T lineage antigens for the therapy of blood malignancies is frequently complicated by self-targeting of CAR T cells or their excessive differentiation driven by constant CAR signaling. Expression of CARs targeting CD7, a pan-T cell antigen highly expressed in T cell malignancies and some myeloid leukemias, produces robust fratricide and often requires additional mitigation strategies, such as CD7 gene editing. In this study, we show fratricide of CD7 CAR T cells can be fully prevented using ibrutinib and dasatinib, the pharmacologic inhibitors of key CAR/CD3ζ signaling kinases. Supplementation with ibrutinib and dasatinib rescued the …

A Spontaneous Nonhuman Primate Model Of Myopic Foveoschisis, Tzu-Ni Sin, Sangbae Kim, Yumei Li, Jun Wang, Rui Chen, Sook Hyun Chung, Soohyun Kim, M Isabel Casanova, Sangwan Park, Zeljka Smit-Mcbride, Ning Sun, Ori Pomerantz, Jeffrey A Roberts, Bin Guan, Robert B Hufnagel, Ala Moshiri, Sara M Thomasy, Paul A Sieving, Glenn Yiu

Faculty, Staff and Students Publications

Purpose: Foveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multimodal imaging followed by morphologic, cellular, and transcriptional profiling of retinal tissues and genetic analysis.

Methods: We identified a rhesus macaque with behavioral and anatomic features of myopic foveoschisis, …

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …

Distribution Pattern Of Antibiotic Resistance Genes In Escherichia Coli Isolated From Colibacillosis Cases In Broiler Farms Of Egypt, Mona A A Abdel-Rahman, Engy A Hamed, May F Abdelaty, Hend K Sorour, Heba Badr, Wafaa M Hassan, Azhar G Shalaby, Ahmed Abd-Elhalem Mohamed, Mohamed A Soliman, Heba Roshdy

Faculty, Staff and Student Publications

BACKGROUND AND AIM: Multidrug resistance (MDR) of

MATERIALS AND METHODS: Samples from 938 broiler farms were bacteriologically examined for

RESULTS:

CONCLUSION: The study showed a high prevalence of

Radiofrequency Ablation Remodels The Tumor Microenvironment And Promotes Neutrophil-Mediated Abscopal Immunomodulation In Pancreatic Cancer, Erika Y Faraoni, Baylee J O'Brien, Lincoln N Strickland, Baron K Osborn, Victoria Mota, Jarod Chaney, Constance Lynn Atkins, Putao Cen, Julie Rowe, Jessica Cardenas, Kyle L Poulsen, Curtis J Wray, Nirav C Thosani, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a 5-year overall survival rate of 11%, despite efforts to improve clinical outcomes in the past two decades. Therapeutic resistance is a hallmark of this disease, due to its dense and suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising local ablative and potential immunomodulatory therapy for PDAC. In this study, we performed RFA in a preclinical tumor-bearing KrasG12D; Trp53R172H/+; Pdx1:Cre (KPC) syngeneic model, analyzed local and abscopal affects after RFA and compared our findings with resected PDAC specimens. We found that RFA reduced PDAC tumor progression in vivo and promoted strong …

Vista Targeting Of T-Cell Quiescence And Myeloid Suppression Overcomes Adaptive Resistance, Evelien Schaafsma, Walburga Croteau, Mohamed Eltanbouly, Elizabeth C Nowak, Nicole C Smits, Jie Deng, Aurelien Sarde, Cecilia A Webber, Dina Rabadi, Chao Cheng, Randolph Noelle, J Louise Lines

Faculty, Staff and Students Publications

VISTA is a premier target for cancer treatment due to its broad expression in many cancer types and enhanced expression upon development of adaptive immune checkpoint resistance. In the CT26 colorectal cancer model, monotherapy of small tumors with anti-VISTA resulted in slowed tumor growth. In a combination therapy setting, large CT26 tumors showed complete adaptive resistance to anti-PD-1/CTLA-4, but inclusion of anti-VISTA led to rejection of half the tumors. Mechanisms of enhanced anti-tumor immunity were investigated using scRNA-seq, multiplex image analysis and flow cytometry of the tumor immune infiltrate. In both treatment models, anti-VISTA upregulated stimulated antigen-presentation pathways and reduced …

Subtype And Site Specific-Induced Metabolic Vulnerabilities In Prostate Cancer, Federica Mossa, Daniele Robesti, Ramachandran Sumankalai, Eva Corey, Mark Titus, Yuqi Kang, Jianhua Zhang, Alberto Briganti, Francesco Montorsi, Christopher P Vellano, Joseph R Marszalek, Daniel E Frigo, Christopher J Logothetis, Taranjit S Gujral, Eleonora Dondossola

Faculty, Staff and Student Publications

Aberrant metabolic functions play a crucial role in prostate cancer progression and lethality. Currently, limited knowledge is available on subtype-specific metabolic features and their implications for treatment. We therefore investigated the metabolic determinants of the two major subtypes of castration-resistant prostate cancer [androgen receptor-expressing prostate cancer (ARPC) and aggressive variant prostate cancer (AVPC)]. Transcriptomic analyses revealed enrichment of gene sets involved in oxidative phosphorylation (OXPHOS) in ARPC tumor samples compared with AVPC. Unbiased screening of metabolic signaling pathways in patient-derived xenograft models by proteomic analyses further supported an enrichment of OXPHOS in ARPC compared with AVPC, and a skewing toward …

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer, Thirumagal Thiyagarajan, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Sarah Asemota, Kirsten L Young, Daniel L Johnson, Vera Bocharova, Weidong Zhou, Abhinav K Jain, Emanuel F Petricoin, Zheng Yin, Lawrence M Pfeffer, Duane D Miller, Ramesh Narayanan

Faculty, Staff and Student Publications

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a …

Microenvironmental Ammonia Enhances T Cell Exhaustion In Colorectal Cancer, Hannah N Bell, Amanda K Huber, Rashi Singhal, Navyateja Korimerla, Ryan J Rebernick, Roshan Kumar, Marwa O El-Derany, Peter Sajjakulnukit, Nupur K Das, Samuel A Kerk, Sumeet Solanki, Jadyn G James, Donghwan Kim, Li Zhang, Brandon Chen, Rohit Mehra, Timothy L Frankel, Balázs Győrffy, Eric R Fearon, Marina Pasca Di Magliano, Frank J Gonzalez, Ruma Banerjee, Daniel R Wahl, Costas A Lyssiotis, Michael Green, Yatrik M Shah

Faculty, Staff and Student Publications

Effective therapies are lacking for patients with advanced colorectal cancer (CRC). The CRC tumor microenvironment has elevated metabolic waste products due to altered metabolism and proximity to the microbiota. The role of metabolite waste in tumor development, progression, and treatment resistance is unclear. We generated an autochthonous metastatic mouse model of CRC and used unbiased multi-omic analyses to reveal a robust accumulation of tumoral ammonia. The high ammonia levels induce T cell metabolic reprogramming, increase exhaustion, and decrease proliferation. CRC patients have increased serum ammonia, and the ammonia-related gene signature correlates with altered T cell response, adverse patient outcomes, and …

Mitochondrial Dysfunction Reactivates Α-Fetoprotein Expression That Drives Copper-Dependent Immunosuppression In Mitochondrial Disease Models, Kimberly A Jett, Zakery N Baker, Amzad Hossain, Aren Boulet, Paul A Cobine, Sagnika Ghosh, Philip Ng, Orhan Yilmaz, Kris Barreto, John Decoteau, Karen Mochoruk, George N Ioannou, Christopher Savard, Sai Yuan, Osama Hmh Abdalla, Christopher Lowden, Byung-Eun Kim, Hai-Ying Mary Cheng, Brendan J Battersby, Vishal M Gohil, Scot C Leary

Faculty, Staff and Students Publications

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by α-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that α-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative …

Antisense Oligonucleotide Therapy Rescues Disturbed Brain Rhythms And Sleep In Juvenile And Adult Mouse Models Of Angelman Syndrome, Dongwon Lee, Wu Chen, Heet Naresh Kaku, Xinming Zhuo, Eugene S Chao, Armand Soriano, Allen Kuncheria, Stephanie Flores, Joo Hyun Kim, Armando Rivera, Frank Rigo, Paymaan Jafar-Nejad, Arthur L Beaudet, Matthew S Caudill, Mingshan Xue

Faculty, Staff and Students Publications

UBE3A encodes ubiquitin protein ligase E3A, and in neurons its expression from the paternal allele is repressed by the UBE3A antisense transcript (UBE3A-ATS). This leaves neurons susceptible to loss-of-function of maternal UBE3A. Indeed, Angelman syndrome, a severe neurodevelopmental disorder, is caused by maternal UBE3A deficiency. A promising therapeutic approach to treating Angelman syndrome is to reactivate the intact paternal UBE3A by suppressing UBE3A-ATS. Prior studies show that many neurological phenotypes of maternal Ube3a knockout mice can only be rescued by reinstating Ube3a expression in early development, indicating a restricted therapeutic window for Angelman syndrome. Here, we …

Follistatin Regulates The Specification Of The Apical Cochlea Responsible For Low-Frequency Hearing In Mammals, Hei Yeun Koo, Min-A Kim, Hyehyun Min, Jae Yeon Hwang, Meenakshi Prajapati-Dinubila, Kwan Soo Kim, Martin M Matzuk, Juw Won Park, Angelika Doetzlhofer, Un-Kyung Kim, Jinwoong Bok

Faculty, Staff and Students Publications

The cochlea's ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region's frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in …

Investigating The Role Of Vasopressin Receptor 1a Expressing Neurons In Mouse Dorsal Raphe, Tirth Nimishbhai Patel

Theses and Dissertations

Human social interactions heavily impact our physical and mental wellbeing. Arginine-vasopressin (Avp) and serotonin have both been implicated in modulation of social behaviors ranging from affiliation to aggression. In male mice, Avp neurons in the bed nucleus of stria terminalis (BNST) show increased activity during prosocial behavior. BNST sends Avp afferents to the dorsal raphe (DR) in the midbrain, a home to a large portion of serotonin neurons in the mouse brain. Previous data suggests that DR is activated during male prosocial behavior with a female stimulus, and Avp indirectly excites serotonin neurons. We hypothesized that DR contains a population …

Effects Of Disulfiram On The Metabolome Of Mrsa, Surya Teja Naidu

Theses, Dissertations and Capstones

Disulfiram, known as Antabuse®, is an oral drug for the treatment of alcohol dependence. Previous studies have indicated that disulfiram (DSF) exhibits antibacterial effects, particularly against Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Our study delves into the antibacterial mechanism of DSF in MRSA through High-Pressure Liquid Chromatography (HPLC) metabolomics, investigating the underlying mechanism of DSF effects on thiamine and amino acid metabolism. Thiamine pyrophosphate (TPP) plays a crucial role as a cofactor for critical enzymes such as transketolase, pyruvate dehydrogenase, and 2-oxoglutarate dehydrogenase. These enzymes are integral to the carbohydrate metabolism process within bacterial cells. TPP also contributes …

Fusion, 2023, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Defining The Nuanced Nature Of Redox Biology In Post-Traumatic Stress Disorder, Emily C. Reed, Adam J. Case

Journal Articles: Cellular & Integrative Physiology

Post-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of …

Evaluation Of Clinical And Radiographic Outcomes Associated With Dental Implants Subjected To Different Loading Protocols, Ahmed Abdel-Halim Hegazy, Mohamed Zaghlool Amer, Wael Mohamed Ahmed, Mohamed Mahmoud Anees

Mansoura Journal of Dentistry

Objective: To evaluate the clinical and radiographic outcomes associated with dental implants subjected to different loading protocols in the posterior maxillary region.

Patients and methods: This clinical study included 16 implants placed in patients seeking the rehabilitation of single/multiple teeth in the posterior maxillary region. The patients were distributed randomly into three groups according to the loading protocol; the 1st group received four implants subjected to conventional loading protocol, the 2nd group received six implants subjected to early loading protocol, additionally the 3rd group received six implants subjected to immediate loading protocol. The evaluation was done immediately after crown cementation …

Early Assessment Of Extremity Compartment Syndrome By Biochemical Markers In A Rat Model, Ahmet Yildirim, İbrahi̇m Özkan Önal, Zeli̇ha Esi̇n Çeli̇k, Hüsametti̇n Vatansev, Esra Paydaş Hataysal

Turkish Journal of Medical Sciences

Background/aim: This experimental study aimed to define a biochemical marker that will enable early diagnosis of acute compartment syndrome (ACS) of extremities, a mortal condition that occurs due to trauma. Materials and methods: A total of 15 Wistar rats were included in the study in which saline infusion technique, a clinically compatible ACS model, was applied. After the rats were anesthetized with ketamine-xylazine, the in-compartment pressure of the hind limb was slowly increased with saline delivered through the angiocatheter, and after reaching the target compartment pressure, the pressure level was kept with a rubber tourniquet. The in-compartment pressure level was …

Effect Of Crocin And Losartan On Biochemical Parameters And Genes Expression Of Frmd3 And Bmp7 In Diabetic Rats, Yaser Mohammadi, Mohammad Zangooei, Fatemeh Salmani, Azam Rezaei Farimani

Turkish Journal of Medical Sciences

Background/aim: Diabetes is a multifactorial and growing disease, one of the severe complications of which is diabetic nephropathy (DN), which is the most common cause of chronic renal failure. FERM domain containing 3 (FRMD3) is responsible for maintaining the shape and integrity of nephron cells, and bone morphogenetic protein 7 (BMP7) helps maintain function and reduce kidney damage. This study aimed to evaluate the effect of crocin and losartan on biochemical parameters and the expression of FRMD3 and BMP7 genes in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Forty male Wistar rats were randomly divided into five experimental groups as …